Teratogenicity of adriamycin and daunomycin in the rat and rabbit.
The antitumor drugs adriamycin and daunomycin were evaluated for effects on embryonal and fetal development in the rat and rabbit. Doses of adriamycin ranging from 1-2 mg/kg/day or daunomycin ranging from 1-4 mg/kg/day were administered ip to pregnant rats on days 6-15, 6-9, 9-12 or 12-15 of gestation. Both drugs were teratogenic in the rat, particularly when administered on days 6-15 or 6-9 of gestation. Relatively few anomalies resulted from treatment on days 9-12 or 12-15. On a mg/kg basis, adriamycin was the more potent teratogen, producing major anomalies at doses as low as 1.25 mg/kg. Similar anomalies, but at a lower incidence, were produced by daunomycin at dose levels of 4 mg/kg. Characteristic malformations included esophageal and intestinal atresia, tracheo-esophgeal fistula, hypoplasia of the urinary bladder and various cardiovascular anomalies. Neither drug was teratogenic when given iv to rabbits at doses up to and including 0.6 mg/kg/day on days 6-18 of gestation, but a high incidence of abortion occurred in rabbits treated with adriamycin.